Rhodopsin-family receptors associate with small G proteins to activate phospholipase D

Rory Mitchell (), Derek McCulloch, Eve Lutz, Melanie Johnson, Chris MacKenzie, Myles Fennell, George Fink, Wei Zhou and Stuart C. Sealfon
Additional contact information
Rory Mitchell: MRC Brain Metabolism Unit
Derek McCulloch: MRC Brain Metabolism Unit
Eve Lutz: MRC Brain Metabolism Unit
Melanie Johnson: MRC Brain Metabolism Unit
Chris MacKenzie: MRC Brain Metabolism Unit
Myles Fennell: MRC Brain Metabolism Unit
George Fink: MRC Brain Metabolism Unit
Wei Zhou: Mount Sinai School of Medicine, New York
Stuart C. Sealfon: Mount Sinai School of Medicine, New York

Nature, 1998, vol. 392, issue 6674, 411-414

Abstract: Abstract G-protein-coupled receptors of the rhodopsin family transduce many important neural and endocrine signals. These receptors activate heterotrimeric G proteins and in many cases also cause activation of phospholipase D, an enzyme that can be controlled by the small G proteins ARF and RhoA1,2,3. Here we show that the activation of phospholipase D that is induced by many, but not all, Ca2+-mobilizing G-protein-coupled receptors is sensitive to inhibitors of ARF and of RhoA. Receptors of this type were co-immunoprecipitated with ARF or RhoA on exposure to agonists, and the effects of GTP analogues on ligand binding to the receptor changed to a profile that is characteristic of small G proteins. These receptors contain the amino-acid sequence AsnProXXTyr in their seventh transmembrane domain, whereas receptors capable of activating phospholipase D without involving ARF contain the sequence AspProXXTyr. Mutation of this latter sequence to AsnProXXTyr in the gonadotropin-releasing hormone receptor conferred sensitivity to an inhibitor of ARF, and the reciprocal mutation in the 5-HT2A receptor for 5-hydroxytryptamine reduced its sensitivity to the inhibitor. Receptors carrying the AsnProXXTyr motif thus seem to form functional complexes with ARF and RhoA.

Date: 1998
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DOI: 10.1038/32937

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